NORADRENALINE NOREPINEPHRINE 1 MG ML Concentrate …

1 MHRA PAR; NORADRENALINE ( NOREPINEPHRINE ) 1 MG / ML Concentrate FOR SOLUTION FOR INFUSION, PL 31980/0001 1 Public Assessment Report Decentralised Procedure NORADRENALINE ( NOREPINEPHRINE ) 1 MG / ML Concentrate for solution for infusion PL 31980/0001 UK/H/1425/01/DC International Drug Licensing MHRA PAR; NORADRENALINE ( NOREPINEPHRINE ) 1 MG / ML Concentrate FOR SOLUTION FOR INFUSION, PL 31980/0001 2 Lay summary The Medicines and Healthcare products Regulatory Agency (MHRA) granted International Drug Licensing a Marketing Authorisation (licence) for the medicinal product NORADRENALINE ( NOREPINEPHRINE ) 1 MG / ML Concentrate for solution for infusion (product licence number: 31980/0001). This medicine is available on prescription only.

2 NORADRENALINE ( NOREPINEPHRINE ) 1 MG / ML Concentrate for solution for infusion belongs to a group of medicines called the adrenergic and dopaminergic agents. NORADRENALINE ( NOREPINEPHRINE ) 1 MG / ML Concentrate for solution for infusion is used to restore normal blood pressure in emergencies when a patient s blood pressure is very low. The data submitted in support of this application for NORADRENALINE ( NOREPINEPHRINE ) 1 MG / ML Concentrate for solution for infusion raised no clinically significant safety concerns and it was therefore judged that the benefits of using this product outweigh the risks; hence a Marketing Authorisation has been granted. MHRA PAR; NORADRENALINE ( NOREPINEPHRINE ) 1 MG / ML Concentrate FOR SOLUTION FOR INFUSION, PL 31980/0001 3 TABLE OF CONTENTS Module 1: Information about decentralised procedure Page 4 Module 2: Summary of Product Characteristics Page 5 Module 3: Product Information Leaflets Page 14 Module 4: Labelling Page 17 Module 5.

3 Scientific Discussion Page 19 1 Introduction 2 Quality aspects 3 Non-clinical aspects 4 Clinical aspects 5 Overall conclusions MHRA PAR; NORADRENALINE ( NOREPINEPHRINE ) 1 MG / ML Concentrate FOR SOLUTION FOR INFUSION, PL 31980/0001 4 Module 1 Information about decentralised procedure Name of the product in the Reference Member State NORADRENALINE ( NOREPINEPHRINE ) 1 MG / ML Concentrate for solution for infusion Type of application (Eudratrack details) Level 1 Abridged Level 2 Initial Level 3 10a Level 4 Chemical substance Level 5 Prescription only Name of the active substance (INN) NORADRENALINE tartrate Pharmacotherapeutic classification (ATC code) Adrenergic and dopaminergic agents (C01CA03)

4 Pharmaceutical form Concentrate for solution for infusion Reference numbers for the decentralised Procedure UK/H/1425/01/DC Reference Member State United Kingdom Member States concerned BE ES Date of start of the procedure 23 June 2008 End date of decentralised procedure 12 January 2010 Marketing Authorisation Number PL 31980/0001 Name and address of the authorisation holder International Drug Licensing 36 avenue Hoche 75008 Paris FRANCE MHRA PAR; NORADRENALINE ( NOREPINEPHRINE ) 1 MG / ML Concentrate FOR SOLUTION FOR INFUSION, PL 31980/0001 5 Module 2 Summary of Product Characteristics 1 NAME OF THE MEDICINAL PRODUCT NORADRENALINE ( NOREPINEPHRINE ) 1 MG / ML Concentrate for solution for infusion 2 QUALITATIVE AND QUANTITATIVE COMPOSITION Each ml of Concentrate for solution for infusion contains 2 mg NORADRENALINE tartrate, equivalent to 1 mg NORADRENALINE base Each 4ml ampoule contains 8mg NORADRENALINE tartrate equivalent to 4mg NORADRENALINE base.

5 Each 8ml ampoule contains 16mg NORADRENALINE tartrate equivalent to 8mg NORADRENALINE base. This medicinal product contains sodium. Each ml of Concentrate for solution for infusion contains mg equivalent to mmol of sodium Each 4ml ampoule contains mg equivalent to mmol of sodium Each 8ml ampoule contains mg equivalent to mmol of sodium To be taken into consideration by patients on a controlled sodium diet. For full list of excipients, see section 3 PHARMACEUTICAL FORM Concentrate for solution for infusion Clear, colourless liquid pH = to 4 CLINICAL PARTICULARS Therapeutic indications NORADRENALINE is indicated for the emergency restoration of blood pressure in cases of acute hypotension.

6 Posology and method of administration Route of Administration: For intravenous use only. NORADRENALINE should be administered through central venous devices to minimize the risk of extravasation and subsequent tissue necrosis. MHRA PAR; NORADRENALINE ( NOREPINEPHRINE ) 1 MG / ML Concentrate FOR SOLUTION FOR INFUSION, PL 31980/0001 6 NORADRENALINE 1mg/ml Concentrate should be diluted prior to intravenous infusion, either with dextrose 5%, or with isotonic dextrose saline. It should not be mixed with other medicines. The final concentration of the infusion solution should be 80 mg/litre NORADRENALINE tartrate, which is equivalent to 40 mg/litre NORADRENALINE base. If other dilutions are used, check the calculation carefully before starting treatment.

7 Dilution instructions: Either add 2 ml of NORADRENALINE 1 MG/ML to 48 ml 5% dextrose (or isotonic dextrose saline) for administration by syringe pump, or add 20 ml of NORADRENALINE 1 MG/ML to 480 ml 5% dextrose (or isotonic dextrose saline) for administration by drip counter. In the both cases the final concentration of the infusion solution is 80 mg/litre NORADRENALINE tartrate, which is equivalent to 40 mg/litre NORADRENALINE base. If other dilutions are used check the calculation carefully before starting treatment. Blood pressure control: Measure blood pressure every two minutes at the beginning of the infusion until the desired blood pressure is obtained. Then every five minutes when desired the blood pressure is obtained, if the administration has to be continued.

8 The infusion should be at a control rate and the patient should be monitored carefully for the duration of NORADRENALINE ( NOREPINEPHRINE ) therapy. Adults: Initial rate of infusion: The initial rate of infusion should be between 10 ml/hour and 20 ml/hour ( ml/min to ml/min). This is equivalent to mg/hr to mg/hr NORADRENALINE tartrate (or mg/hr to mg/hr NORADRENALINE base). Titration of dose: Once an infusion of NORADRENALINE has been established the dose should be titrated according to the pressor effect observed. There is great individual variation in the dose required to attain and maintain normotension. The aim should be to establish a low normal systolic blood pressure (100-120 mm Hg) or to achieve an adequate mean arterial blood pressure (greater than 65 to 80 mm Hg depending on the patient s condition).

9 NORADRENALINE tartrate Infusion solution at 80 mg/L Patient s Weight Posology ( g/kg/min) Tartrate Posology (mg/h) Tartrate Infusion rate (ml/h) 9 1 45 60 kg 2 90 MHRA PAR; NORADRENALINE ( NOREPINEPHRINE ) 1 MG / ML Concentrate FOR SOLUTION FOR INFUSION, PL 31980/0001 1 70 kg 2 105 12 30 1 60 80 kg 2 120 h: hour If other dilutions are used check the calculation carefully before starting treatment.

10 Duration of Treatment and Monitoring: NORADRENALINE should be continued for as long as vasoactive drug support is indicated. The patient should be monitored carefully for the duration of NORADRENALINE therapy. The infusion must not be stopped suddenly but should be gradually withdrawn to avoid disastrous falls in blood pressure. Elderly: As for adults but see Precautions. Children: Not recommended Contraindications Use of NORADRENALINE 1 mg/ml Concentrate for solution for infusion is contraindicated in patients with known hypersensitivity to NORADRENALINE or to any of the excipients. Hypotension due to blood volume deficit (Hypovolaemia) The use of pressor amines during cyclopropane or halothane anaesthesia may cause serious cardiac arrhythmias.